Equine infectious anemia virus (EIAV) is a lentivirus of horses causing persistent infection. In contrast to lentivirus infections in other species, notably human immunodeficiency virus-1 (HIV-1), most horses, although chronically infected, enter a life-long inapparent carrier state with no further occurrences of clinical symptoms, and no obvious impairment of health and physical ability. The overall goal of the proposed research is to further dissect the roles of helper and cytotoxic T lymphocytes in the control of initial EIAV infection and maintenance of the inapparent carrier state. To that end, the experiments outlined in this proposal will directly test the hypothesis that induction of a viral-specific Th1 CD4+ lymphocyte response, directed toward conserved EIAV epitopes, will promote enhanced CTL responses to, and afford protection against, subsequent EIAV challenge. Specific aim 1 seeks to identify universal CD4+ Th1 epitopes located in conserved regions of the EIAV genome by mapping proliferative responses to peptides by CD4+ memory T lymphocytes of EIAV-infected long-term inapparent carrier horses. Specific aim 2 is to induce a CD4+ Th1 response in nave horses after immunization with lipopeptide versions of the universal epitopes identified in Aim 1. Specific aim 3 is to measure the protective effects of immunization with viral-specific CD4+ Th1 epitopes to subsequent challenge with EIAV.